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The role of melatonin and carnosine in prevention of oxidative intestinal injury induced by gamma irradiation in rats

  • Omur Karabulut-Bulan EMAIL logo , Huseyin Us , Bertan Boran Bayrak , Ayca Sezen-Us and Refiye Yanardag
Published/Copyright: August 31, 2017
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Abstract

Exposure of biological materials to ionizing irradiation causes accumulation of reactive oxygen species. The current study aimed to investigate whether melatonin or carnosine could provide protection against irradiation-induced small intestinal damage. Forty Wistar albino rats were divided into five groups. Melatonin, carnosine, and combination of carnosine and melatonin were injected into rats in the third, fourth, and fifth groups, respectively. Rats were injected three times every 48 hours. All groups, excluding the control group, were exposed to a dose of 8 Gray whole body gamma irradiation one hour after the second injection. It was determined that irradiation caused degenerative changes in the intestinal tissues, reduced PCNA (proliferating cell nuclear antigen) -positive cell number, and increased caspase-3- and TNF-α (tumour necrosis factor alpha) -positive crypt cell numbers. Results obtained from antioxidant-treated groups were similar to those from the control group. Lipid peroxidation and protein carbonyl levels as well as superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, myeloperoxidase, lactate dehydrogenase and xanthine oxidase activities were increased. However, catalase, sodium potassium ATPase activities and glutathione levels were decreased in the irradiated group of animals. Treatment with antioxidants reversed these changes. It is suggested that exogenous melatonin, carnosine, and melatonin+carnosine combination exhibit protective effects against irradiation-induced small intestinal damage.

Acknowledgements

This study was supported by The Scientific Research Projects Coordination Unit of Istanbul University (Project No: 18248; BYP: 54474; UDP: 57652).

References

Abou-Seif M.A.M., El-Naggar M.M., El-Far M., Ramadan M. & Salah N.2003. Amelioration ofradiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated gamma-irradiated rats. Clin. Chim. Acta 337(1-2): 23–33. 10.1016/S0009-8981(03)00192-XSearch in Google Scholar

Akpolat M. 2007. Gamma radyasyonun ileum kadehsi hücrelerinde oluşturduğu hasarlara karşıcurcumin ve c vitamininin koruyucu etkilerinin ışık ve elektron mikroskobik düzeylerde incelenmesi [Examining the protective effects of curcumin and vitamin c against gamma radiation-induced ileum goblet cell damage at light and electron microscopic levels]. PhD Thesis, Trakya University, Edirne, Turkey, 88 pp.Search in Google Scholar

Aydin A.F, Kucukgergin C., Ozdemirler-Erata G., Kocak-Toker N. & Uysal M. 2010a. The effect of carnosine treatment on prooxidant-antioxidant balance in liver, heart and brain tissues of male aged rats. Biogerontology 11 (1): 103–109. 10.1007/s10522-009-9232-4Search in Google Scholar

Aydin A.F., Kusku-Kiraz Z., Dogru-Abbasoglu S., Gulluoglu M., Uysal M. & Kocak-Toker N. 2010b. Effect of carnosine against thioacetamide-induced liver cirrhosis in rat. Peptides 31 (1): 67–71. 10.1016/j.peptides.2009.11.028.Search in Google Scholar

Babizhayev M.A., Seguin M.C., Gueyne J., Evstigneeva R.P., Ageyeva E.A. & Zheltukhina G.A. 1994. L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem. J. 304 (Pt.2): 509–516. 10.1042/bj3040509Search in Google Scholar PubMed

Brzezinski A. 1997. Melatonin in humans. N. Engl. J. Med. 336 (3): 186–195. 10.1056/NEJM199701163360306Search in Google Scholar PubMed

Carney J.M. & Carney A.M. 1994. Role of protein oxidation in aging and in age-associated neurodegenerative diseases. Life Sci. 55 (25-26): 2097–2103. 10.1016/0024-3205(94)00390-4Search in Google Scholar PubMed

Carroll M.P., Zera R.T., Roberts J.C., Schlafmann S.E., Feeney D.A., Johnston G.R., West M.A. & Bubrick M.P. 1995. Efficacy of radioprotective agents in preventing small and large bowel radiation injury. Dis. Colon Rectum 38 (7): 716–722. 10.1007/BF02048028Search in Google Scholar PubMed

Chan W.K.M., Decker E.A., Lee J.B. & Butterfield L.D. 1994. EPR spin-trapping studies of the hydroxy radical scavenging activity of carnosine and related dipeptides. J. Agric. Food Chem. 42 (7): 1407–1410. 10.1021/jf00043a003Search in Google Scholar

Chavan S., Sava L., Saxena V., Pillai S., Sontakke A. & Ingole D. 2005. Reduced glutathione: importance of specimen collection. Indian J. Clin. Biochem. 20 (1): 150–152. 10.1007/BF02893062.Search in Google Scholar PubMed PubMed Central

Corte E.D. & Stirpe F. 1968. Regulation of xanthine oxidase in rat liver: modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees. Biochem. J. 108 (2): 349–351. 10.1042/bj1080349Search in Google Scholar PubMed PubMed Central

Fernandez M., Medina A., Santos F., Carbajo E., Rodriguez J., Alvarez J. & Cobo A. 2001. Exacerbated inflammatory response induced by insulin-like growth factor-I treatment in rats with ischemic acute renal failure. J. Am. Soc. Nephrol. 12 (9): 1900–1907. PMID: 1151878310.1681/ASN.V1291900Search in Google Scholar PubMed

Fouad A.A., Qureshi H.A., Yacoubi M.T. & Al-Melhim W.N. 2009. Protective role of carnosine in mice with cadmium-induced acute hepatotoxicity. Food Chem. Toxicol. 47 (11): 2863–2870. 10.1016/j.fct.2009.09.009.Search in Google Scholar PubMed

Fujii T., Takaoka M., Muraoka T., Kurata H., Tsuruoka N., Ono H., Kiso Y., Tanaka T. & Matsumura Y. 2005. Dietary supplementation of L-carnosine prevents ischemia/reperfusion induced renal injury in rats. Biol. Pharm. Bull. 28 (2): 361–363. 10.1248/bpb.28.361Search in Google Scholar PubMed

Giris M., Erbil Y., Oztezcan S., Olgac V., Barbaros U., Deveci U., Kirgiz B., Uysal M. & Toker G.A. 2006. The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oygenase-1 on radiation enteritis. Am. J. Surg. 191 (4): 503–509. 10.1016/j.amjsurg.2005.11.004Search in Google Scholar

Habig W.H. & Jacoby W.B. 1981. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 77: 398–405. 10.1016/S0076-6879(81)77053-8Search in Google Scholar PubMed

Haeri S.A., Rajabi H., Fazelipour S. & Hosseinimehr S.J. 2014. Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice. Andrologia 46 (9): 1041–1046. 10.1111/and.12193Search in Google Scholar PubMed

Hussein M.R., Abu-Dief E.E., Kamel E., El-Ghait A.T.A., Abdulwahed S.R. & Ahmad M.H. 2008. Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: An animal model. Cell Biol. Int. 32 (11): 1353–1361. 10.1016/j.cellbi.2008.08.001Search in Google Scholar PubMed

Javois L.C. (ed.). 1999. Immunocytochemical Methods and Protocols. 2nd ed. Series: Methods in Molecular Biology, Vol. 115. Humana Pres, Totowa, New Jersey, 465 pp. ISBN-10: 0-89603-570-0, ISBN-13: 978-0-89603-570-6Search in Google Scholar

Kanter M., Tarladaçalışır Y.T., Akpolat M. & Mercantepe T. 2008. Gamma radyasyona bağlıoluşan jejunum mukoza hasarina karşı curcumin ve amifostinin koruyucu etkilerinin incelenmesi [Protective effect of curcumin and amifostine on gamma radiation-induced jejunal mucosal damage in rats]. Tıp Araştırmaları Dergisi 6 (3): 128–135.Search in Google Scholar

Karabulut-Bulan O., Bayrak B.B., Arda-Pirincci P., Sarikaya-Unal G., Us H. & Yanardag R. 2015. Role of exogenous melatonin on cell proliferation and oxidant/antioxidant system in aluminum-induced renal toxicity. Biol. Trace Elem. Res. 168 (1): 141–149. 10.1007/s12011-015-0320-9Search in Google Scholar PubMed

Karbownik M. & Reiter R.J. 2000. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc. Soc. Exp. Biol. Med. 225 (1): 9–22. PMID: 1099819410.1046/j.1525-1373.2000.22502.xSearch in Google Scholar PubMed

Klucinski P., Wójcik A., Grabowska-Bochenek R., Gmiński J., Mazur B., Hrycek A., Cieślik P. & Matirosian G. 2008. Erythrocyte antioxidant parameters in workers occupationally exposed to low levels of ionizing radiation. Ann. Agric. Environ. Med. 15 (1): 9–12. PMID: 18581973Search in Google Scholar PubMed

Kunwar A., Bag P.P., Chattopadhyay S., Jain V.K. & Priyadarsini K.I. 2011. Anti-apoptotic, anti-inflammatory, and immunomodulatory activities of 3,3-diselenodipropionic acid in mice exposed to whole body γ-radiation. Arch. Toxicol. 85 (11): 1395–1405. 10.1007/s00204-011-0687-0Search in Google Scholar PubMed

Lebrun F., Francois A., Vergnet M., Lebaron-Jacobs L., Gourmelon P. & Griffiths N.M. 1998. Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function. Am. J. Physiol. 275 (6 Pt.1): G1333–G1340. PMID: 984377010.1152/ajpgi.1998.275.6.G1333Search in Google Scholar

Ledwozyw A., Michalak J., Stepień A. & Kadziołka A. 1986. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin. Chim. Acta 155 (3): 275–283. 10.1016/0009-8981(86)90247-0Search in Google Scholar PubMed

Lentsch A.B., Atsushi K. & Yoshidome H. 2000. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 32 (2): 169–173. 10.1053/jhep.2000.9323Search in Google Scholar PubMed

Levine R.L., Garland D., Oliver C.N., Amici A., Climent I., Lenz A.G., Ahn B.W., Shaltiel S. & Stadtman E.R. 1990. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 186: 464–478. 10.1016/0076-6879(90)86141-HSearch in Google Scholar PubMed

Lowry O.H., Rosebrough N.J., Farr A.L. & Randall R.J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193 (1): 265–275. PMID: 1490771310.1016/S0021-9258(19)52451-6Search in Google Scholar PubMed

Mohseni M., Mihandoost E., Shirazi A., Sepehrizadeh Z., Bazzaz J.T. & Ghazikhansari M. 2012. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis. Mutat. Res. 738-739: 19–27. 10.1016/j.mrfmmm.2012.08.006Search in Google Scholar PubMed

Monobe M., Hino M., Sumi M., Uzawa A., Hirayama R. & Ando K. 2005. Protective effect of melatonin on γ-ray induced intestinal damage. Int. J. Radiat. Biol. 81 (11): 855–860. 10.1080/09553000600554804Search in Google Scholar PubMed

Mylroie A.A., Collins H., Umbles C. & Kyle J. 1986. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol. Appl. Pharmacol. 82 (3): 512–520. 10.1016/0041-008X(86)90286-3Search in Google Scholar PubMed

Neoman E., Zahran A.M. & Kamal A.M. 2002. Vitamin E and selenium administration as a modulator of antioxidant defence system: Biochemical assesment and modification. Biol. Trace Elem. Res. 86 (1): 55–64. 10.1385/BTER:86:1:55Search in Google Scholar

Noori S. & Mahboob T. 2010. Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats. Indian J. Clin. Biochem. 25 (1): 86–91. 10.1007/s12291-010-0018-xSearch in Google Scholar PubMed

Onal C., Kayaselcuk F., Topkan E., Yavuz M., Bacanli D. & Yavuz A. 2011. Protective effects of melatonin and octreotide against radiation-induced intestinal injury. Dig. Dis. Sci. 56 (2): 359–367. 10.1007/s10620-010-1322-2Search in Google Scholar PubMed

Ozalpan A.2001. Temel Radyobiyoloji [Basic Radiobiology]. 1st ed. Halic University Publication, Istanbul, 353 pp. ISBN: 9758574000, 9789758574001Search in Google Scholar

Paglia D.E. & Valentine W.N. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70 (1): 158–169. PMID: 6066618Search in Google Scholar PubMed

Potten C.S., Merritt A., Hickman J., Hall P. & Faranda A. 1994. Characterization of radiation-induced apoptosis in the small intestine and its biological implications. Int. J. Radiat. Biol. 65 (1): 71–78. 10.1080/09553009414550101Search in Google Scholar PubMed

Pratheeshkumar P. & Kuttan G. 2011. Protective role of Vernonia cinerea L. against gamma-radiation-induced immunosuppression and oxidative stress in mice. Hum. Exp. Toxicol. 30 (8): 1022–1038. 10.1177/0960327110385959Search in Google Scholar PubMed

Reiter R.J., Tan D.X., Mayo J.C., Sainz R.M., Leon J. & Czarnocki Z. 2003. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim. Pol. 50 (4): 1129–1146. 0350041129Search in Google Scholar PubMed

Ridderstap A.S. & Bonting S.L. 1969. Na+-K+ activated ATPase and exocrine pancreatic secretion in vitro. Am. J. Physiol. 217 (6): 1721–1727.10.1152/ajplegacy.1969.217.6.1721Search in Google Scholar PubMed

Saada H.N., Rezk R.G. & Eltahawy N.A. 2010. Lycopene protects the structure of the small intestine against gamma-radiation-induced oxidative stress. Phytother. Res. 24 (Suppl. 2): S204–S208. 10.1002/ptr.3091Search in Google Scholar

Saclarides T.J. 1997. Radiation injuries of the gastrointestinal tract. Surg. Clin. N. Am. 77 (1): 261–268. 10.1016/S0039-6109(05)70544-2Search in Google Scholar

Sainza R.M., Mayo J.C., Rodriguez C., Tan D.X., Lopez-Burilloa S. & Reiter R.J. 2003. Melatonin and cell death: differential actions on apoptosis in normal and cancer cells. Cell. Mol. Life Sci. 60 (7): 1407–1426. 10.1007/s00018-003-2319-1Search in Google Scholar PubMed

Samarth R.M. & Kumar A. 2003. Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice. Indian J. Exp. Biol. 41 (3): 229–237. PMID: 15267153Search in Google Scholar PubMed

Schulze-Osthoff K. 2008. Apoptosis, cytotoxicity and cell proliferation, pp. 2–15. In: Rode H.J., Eisel D. & Frost I. (eds), Roche Applied Science: Apoptosis, Cell Death and Cell proliferation, 4th edn, Roche Diagnostics GmbH, Mannheim 186 pp.Search in Google Scholar

Sener G., Jahovic N., Tosun O., Atasoy B.M. & Yegen B.C. 2003. Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats. Life Sci. 74 (5): 563–572. 10.1016/j.lfs.2003.05.011Search in Google Scholar PubMed

Sert C. & Çelik M.S. 1996. Radyasyondan koruyucu ajanlar [Radioprotective agents]. Türkiye Klinikleri J. Med. Sci. 16 (4): 292–298.Search in Google Scholar

Sheen-Chen S., Ho H., Chen W. & Eng H. 2003. Obstructive jaundice alters proliferating cell nuclear antigen expression in rat small intestine. World J. Surg. 27 (10): 1161–1164. 10.1007/s00268-003-6992-xSearch in Google Scholar PubMed

Somosy Z., Horvath M., Telbisz A., Rez G. & Palfia Z. 2002. Morphological aspects of ionizing radiation response of small intestine. Micron 33 (2): 167–178. 10.1016/S0968-4328(01)00013-0Search in Google Scholar PubMed

Srivastava M., Chandra D. & Kale R.K. 2002. Modulation of radiation-induced changes in the xanthine oxidorecustase system in the livers of mice by its inhibitors. Radiat. Res. 157 (3): 290–297. PMID: 1183909110.1667/0033-7587(2002)157[0290:MORICI]2.0.CO;2Search in Google Scholar PubMed

Take G., Erdogan D., Helvacioglu F., Göktas G., Ozbey G., Uluoglu C., Yücel B., Guney Y., Hicsonmez A. & Ozkan S. 2009. Effect of melatonin and time of administration on irradiation-induced damage to rat testes, effects of melatonin on irradiated testes. Braz. J. Med. Biol. Res. 42 (7): 621–628. PMID: 1957864110.1590/S0100-879X2009000700006Search in Google Scholar PubMed

Tanaka R.A., Ramos F.M.M., Almeida S.M., Vizioli M.R. & Bóscolo F.N. 2005. Evaluation of radioprotecive effect of carnosine (β-Alanyl-1-Histidine) on the wound healing in rats. J. Appl. Oral Sci. 13 (3): 253–258. 10.1590/S1678-77572005000300010Search in Google Scholar

Wei H. & Frenkel K. 1993. Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoter. Carcinogenesis 14 (6): 1195–1120. 10.1093/carcin/14.6.1195Search in Google Scholar PubMed

Wendel A. 1981. Glutathione peroxidase. Methods Enzymol. 77: 325–333. 10.1016/S0076-6879(81)77046-0Search in Google Scholar PubMed

Wroblewski F. 1957. Clinical significance serum enzyme alterations associated with myocardial infarction. Am. Hearth J. 54 (2): 219–224. 10.1016/0002-8703(57)90149-7Search in Google Scholar

Yan S.L., Wu S.T., Yin M.C., Chen H.T. & Chen H.C. 2009. Protective effects from carnosine and histidineon acetaminophen-induced liver injury. J. Food Sci. 74 (8): 259–265. 10.1111/j.1750-3841.2009.01330.xSearch in Google Scholar

Yazıcı C. & Köse K. 2004. Melatonin: Karanlığın antioksidan gücü [Melatonin: The antioxidant power of darkness]. Erciyes Üniversitesi Sağlık Bilimleri Dergisi / Erciyes Univ. J. Health Sci. 13 (2): 56–65.Search in Google Scholar

Received: 2017-2-5
Accepted: 2017-5-12
Published Online: 2017-8-31
Published in Print: 2017-8-28

© 2017 Institute of Zoology, Slovak Academy of Sciences

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